The overall objective of this proposal is to investigate methods for enhancing the preferential heating of tumors during hyperthermia treatment. One means of accomplishing this aim was suggested by our previous microwave absorption studies. These investigations indicated that over the frequency range of 150 to 400 MHz, the SMT-2A mammary tumor preferentially absorbed microwave energy when compared to both normal mammary gland tissue and skeletal muscle. In this application, we propose to use a HP 8754A network analyzer to accurately measure the conductivity (Sigma) and permittivity (Epsilon) of normal (skeletal muscle, white adipose tissue and liver) and malignant (mammary adenocarcinoma, lymphoma and hepatoma) tissue as a function of microwave frequency (50-915 MHz) and tissue temperature (37 to 45 degrees C). These values of Sigma and Epsilon will be used to estimate the malignant-to-normal tissue power absorption ratio as a function of frequency in order to determine precisely at which frequencies the absorption of microwaves in malignant tissue maximizes. Additionally, these optimal frequencies will be confirmed by an independent experimental technique which relies upon estimating the initial slope of tissue heating-curves. The results of these two independent experimental approaches will enable us to determine unequivocally which electromagnetic frequencies are optimal for the selective heating of tumors. The absorption of microwaves would also be enhanced by experimental techniques which cause an increase in the ionic conductivity of the tumor. This will be accomplished by injecting ionic salt solutions intratumorally before and during microwave heating, and the effectiveness of this approach in selectively increasing the tumor temperature will be determined. The possibility also exists for increasing the temperature differential between malignant and normal tissue by modifying tumor blood flow, either directly with vasoactive agents which act on the tumor vessels or indirectly with drugs which affect the vessels in the surrounding normal tissue. Preliminary data obtained in the previous grant period indicate that norepinephrine, sodium nitroprusside, and 5-hydroxytryptamine substantially reduce (greater than 50%) tumor blood flow, thereby resulting in a preferential increase in the tumor temperature. Additionally, when utilized at concentrations well tolerated by humans, the calcium entry blockers, verapamil and flunarizine, increase both primary and metastatic tumor blood flow by 50%. Thus, we have evidence that there are vasoactive drugs which can either selectively increase or decrease tumor blood flow. The importance of these vasoactive agents as adjuvants to both localized hyperthermia treatment and conventional treatment modalities will be ascertained during the next grant period.